JPH0372216B2 - - Google Patents

Description

[Detailed description of the invention]

6-methyl-3,4-dihydro-1,2,3-
Oxathiazin-4-one-2,2-dioxide is a compound represented by the following formula: As a result of acidic hydrogen on the nitrogen atom, this compound is
Can form salts (with bases). Non-toxic salts - e.g.
Such as Na, K and Ca salts can be used as sweeteners in the food industry due to their sweetness, in some cases strong sweetness, where K-salts (“Acesulfam K”)
Of particular interest are 6-methyl-3,4-dihydro-1,2,3-
A number of different methods are known for the production of oxathiazin-4-one-2,2-dioxide and its non-toxic salts: for example Angewandte Chemie 85 , No. 22 (1973). , pp. 965-73, equivalent to International Edition Vol. 12, No. 11 (1973), pp. 869-76). Practically all processes start from chlorosulfonyl or fluorosulfonyl isocyanate (XSO ₂ ^- NCO, X=Cl or F). The chlorosulfonyl or fluorosulfonyl isocyanate is then reacted (often in a multistep reaction) with monomethylacetylene, acetone, acetoacetic acid, tert-butyl acetoacetate or benzylpropenyl ether to form acetoacetamide-N-sulfochloride. or acetoacetamide-N-sulfofluorides, which cyclize under the influence of a base (e.g. methanolic KOH) and 6-
This gives the corresponding salt of methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide. Free oxathiazinone is
If desired, these salts can be obtained in the usual manner (with acids). Another method for preparing the oxathiazinone-intermediate step acetoacetamide-N-sulfofluoride starts from the partial hydrolysis product of fluorosulfonylisocyanate, amidosulfofluoride H ₂ NSO ₂ F (German patent application (See Publication No. 2453063). The amidosulfonic acid fluoride, H ₂ NSO ₂ F, is then reacted with approximately equimolar amounts of the acetoacetylating agent, diketene, in the presence of an amine in an inert organic solvent at temperatures of about -30 to 100°C. It will be done. The reaction proceeds according to the following equation (using triethylamine as the amine): The acetoacetamide-N-sulfofluoride is then cyclized in the usual manner with a base, e.g. methanolic KOH, to give the sweetener: These known methods use 6-methyl-3,4-
Although the presence of dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide and its non-toxic salts gives quite satisfactory yields (the theory for the starting material amidosulfonic acid halide) There is still room for improvement, especially for industrial purposes, since it is necessary to use the starting materials chlorsulfonyl or fluorosulfonyl isocyanate, which are not very easily available (up to about 85% of Starting materials that are rather unpleasant to handle (HCN,
Cl ₂ , SO ₃ and HF), the production of chlorosulfonyl and fluorosulfonyl isocyanates requires considerable precautionary measures and safety measures. The production of chlorosulfonyl and fluorosulfonyl isocyanates is based on the following reaction equation: HCN+Cl ₂ →ClCN+HCl ClCN+SO ₃ →ClSO ₂ NCO ClSO ₂ NCO+HF→FSO ₂ NCO+HCl Replacing the fuamoyl fluoride by, for example, the fairly easily obtained (e.g. from NH ₃ +SO ₃ ) amidosulfonic acid H ₂ NSO ₃ H or its salts seems to have little chance of success. . That is, the reaction of sodium amidosulfonate H ₂ NSO ₃ Na with diketene in aqueous alkaline solution does not result in any reaction product that can be isolated in pure form. Rather, it was only possible to isolate the 1:1 adduct, which probably occurs at least in this reaction, in the form of a coupling product with 4-nitrophenyldiazonium chloride as a pale yellow dye; for example, Berichte et al. (Ber.) 83 (1950),
See pp. 551-558, especially the last section before the experimental description on page 555, and the last section on page 558: Furthermore, acetoacetamido-N-sulfonic acid is otherwise 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-
It was considered only or as an intermediate product during the decomposition of 2,2-dioxide by boiling in aqueous solution: first cited in Angew. Chemie (1973), supra. Refer to: 6-methyl-3,4-dihydro-1,2,3-
The prior art processes for producing oxathiazin-4-one-2,2-dioxide and its non-toxic salts are particularly difficult to carry out on an industrial scale, especially when using starting materials that are not readily available. Because of the need for use, the problem arose to suitably improve known methods or to develop new and improved methods. To solve this problem, the method according to German Patent Application No. 2453063 was modified by replacing the amidosulfofluoride in the known process by a salt of amidosulfonic acid and then converting the acetoacetylated product obtained to SO ₃ A major modification has already been proposed: cyclization by (European patent application No. 85102885.2 - Publication
0155634 - Priority: see German patent application P3410439.9 - Japanese Patent Application No. 60-54717 of March 22, 1984). The last-mentioned patent application specifically mentions 6-methyl-
In producing 3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide and its nontoxic salts, (a) the amidosulfonic acid derivative is mixed with at least an equivalent molar amount of acetoacetyl; acetoacetamide derivative, and (b) cyclizing the acetoacetamide derivative. The method comprises: in step (a) using a salt of amidosulfonic acid, at least partially soluble in the inert organic solvent used as the amidosulfonic acid derivative; Step acetoacetamide-N-sulfonate or free acetoacetamide-N-sulfonic acid.
(b) 6-methyl-3,4-dihydro-1,2,3-oxathiazine by the action of at least an equimolar amount of SO ₃ , optionally in an inert inorganic or organic solvent. -4-on-
cyclization to give the 2,2-dioxide, and the product here obtained in acid form is then optionally further neutralized with a base in step (c). . The reaction equation on which the method is based in the above patent application (using diketene as the acetoacetylating agent) is described below: In this reaction scheme, step (b) is shown with an equimolar amount of SO ₃ relative to the acetoacetamide-N-sulfonate. however,
Preferably, an excess amount of SO ₃ is used. In this process, an intermediate product is formed whose chemical structure is still not precisely known, but it is probably 6-methyl-3,4-dihydro-1,
The SO ₃ adduct of 2,3-oxathiazin-4-one-2,2-dioxide, hereinafter referred to as "SO ₃ adduct", is formed, which then has to be further hydrolyzed. In this case, reaction step (b) above thus consists of two substages as follows: The cyclization reaction (b1) is carried out at a temperature of about -70 to +175°C, preferably about -40 to +10°C, according to the method described in the above-mentioned patent application. The reaction time is about 1 hour to 10 hours. Hydrolysis (b2) is carried out by adding water or ice after the cyclization reaction. Purification is then carried out in the customary manner; however, the purification will only be described in detail in the case where methylene chloride is preferably used as reaction medium. In this case, after hydrolysis 2
A phase is formed in which 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-
2,2-dioxide occurs primarily in the organic phase. The portion still present in the aqueous sulfuric acid solution can be recovered by extraction with an organic solvent (immiscible with water), such as, for example, methylene chloride or an organic ester. Alternatively, after adding water, the reaction medium is distilled off and the 6-methyl-
3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide is extracted using a more suitable organic solvent. The combined organic phases are dried, for example with Na ₂ SO ₄ and concentrated. Sulfuric acid, which may have been entrained in the extraction, can be removed by controlled addition of aqueous alkaline solution to the organic phase. 6-methyl-3,4-dihydro-1,2,
If it is desired to isolate 3-oxathiazin-4-one-2,2-dioxide, it is also expedient to purify it in the usual manner, preferably by recrystallization. The yield is about 70 to 95% of theory in terms of acetoacetamido-N-sulfonate (or free acid). However, 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,
If it is intended to isolate non-toxic salts of 2-dioxide, a neutralization step (c) is also carried out.
This is carried out by neutralizing the oxathiazinone compound obtained in the acid form in step (b) with a compatible base in the usual manner. For this purpose, for example, the combined, dried and concentrated organic phases at the end of step (b) can be combined with alcohol, e.g.
neutralization with a suitable base, preferably a potassium base such as KOH, KHCO ₃ , K ₂ CO ₃ , K-alcolate etc. in a suitable organic solvent such as a ketone, ester or ether or also water. be harmonized. Alternatively, the oxathiazinone compound is
The purified organic extract phase (step (b)) is directly extractively neutralized with aqueous potassium base. The oxathiazinone salt is then obtained in crystalline form, optionally after concentration of the solution, and can be further recrystallized for purification. The stage of neutralization passes with practically 100% yield. For further details of this method, reference is made to the description of the above-mentioned patent application. The above method starts from readily available and inexpensive starting materials and can be carried out very simply. The yield of the entire process is about 65 to 95% of theory with respect to the starting amide sulfonate. Regarding the other operations of the above process, both the cyclization reaction (b1) and the hydrolysis (b2) can be carried out within a short to very short time (approximately 10 minutes to seconds and fractions of 1 second). (see German application P3527070.5 of July 29, 1985).The implementation of the above method preferably proceeds rapidly and is accompanied by the generation of heat. Known equipment suitable for carrying out the reaction (thin film reactor, falling film reactor, spray reactor,
It is carried out in a tubular reactor (with or without internal fittings). Purification of the reaction mixture is carried out as described in the specification of the aforementioned patent application. This "short-time variation" enables technical operation and, in particular, significantly improves the space-time yield of the process. Finally, the aforementioned European patent application no.
As an alternative to steps (a) and (b) of the process according to 85102885.2, it has also already been possible to react the acetoacetamide with at least an approximately 2-molar amount of SO ₃ , optionally in an inert inorganic or organic solvent. Proposed (German patent application P3410440.2 (March 1984)
(filed on the 22nd) (see Japanese Patent Application Laid-Open No. 60-54718). In this case, in one step, the _{acetoacetamide--}
N-sulfonic acid is formed which is then further cyclized with 1 mole of SO ₃ according to the reaction scheme below to give 6-methyl-3,4-dihydro-1,
2,3-oxathiazin-4-one-2,2-dioxide: In this case too, the excess SO ₃ causes “SO ₃
6-methyl-
Further hydrolysis must be carried out to liberate 3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide. Purification of the hydrolyzed mixture and optionally conversion of 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide into its non-toxic salts. is carried out in principle in the same manner as described in the aforementioned European Patent Application No. 85102885.2. 6-methyl-
The numerical value of the yield of 3,4-dihydro-1,2,3-oxathiazine-4-2,2-dioxide is approximately 30% of the theoretical amount with respect to the starting material acetoacetamide.
or 90%. According to all three patent applications mentioned above,
6- liberated by hydrolysis of “SO ₃ adduct”
Methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide is
It is obtained from the organic phase which is formed after the addition of water if an organic solvent (immiscible with water) is used in the reaction and/or which is formed if the reaction sulfuric acid is extracted with an organic solvent. However, the 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2, thus obtained,
Since 2-dioxide and the non-toxic salts obtained therefrom optionally by reaction with suitable bases do not necessarily have the required purity,
Purification operations, preferably recrystallization, are often required, with various additional costs and losses of material. The possibility mentioned in European Patent Application No. 85102885.2 of obtaining oxathiazinone compounds by extractive neutralization with aqueous potassium base from a purified organic extract phase is explained in more detail in particular in Example 11 in that patent specification. has been done. There, an aqueous solution of caustic soda is used for the purpose of neutralizing the entrained sulfuric acid in order to purify the organic extraction phase. By further developing these methods described above, we have now treated the organic phase - obtained as described above - with a relatively small amount of water or dilute aqueous sulfuric acid before further purification. 6-methyl-3,4-dihydro-1,2,
It has been found that purer salts of 3-oxathiazin-4-one-2,2-dioxide are obtained. Therefore, the solution of the present invention is to cyclize the acetoacetamide derivative and neutralize it with a base.
A method for producing a non-toxic salt of methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide, which is immiscible with water as an acetoacetamide derivative. acetoacetamide dissolved in an inert organic solvent of
The cyclization is carried out by using an N-sulfonic acid or a salt thereof, dissolved in at least about equimolar amounts of SO ₃ - optionally an inert organic solvent or an inert inorganic solvent which is also immiscible with water. If more than equimolar amounts of SO ₃ are used,
After the cyclization reaction, hydrolyzing the 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide obtained as SO ₃ adduct, present or Purifying the organic phase that separates during hydrolysis by extraction with a relatively small amount of water or dilute aqueous sulfuric acid, and from the organic phase so purified by neutralization with a base, the 6-methyl-3 ,4-dihydro-1,2,3-oxathiazin-4-one-2,
Obtaining a non-toxic salt of 2-dioxide. It is quite surprising that the cyclization of acetoacetamido-N-sulfonic acid and its salts with _SO3 is successful and smooth. because,
As could already be shown by means of a comparative example (using P ₂ O ₅ ) in the above-mentioned European Patent Application No. 85102885.2, the separation of water or base carried out upon cyclization, i.e. for example P ₂ O ₅ , acetic anhydride,
Separation of water or base using other agents for separating water or base, such as trifluoroacetic anhydride, thionyl chloride, etc., is unsuccessful or in any case not successful for practical purposes. Furthermore, 6-methyl- obtained by this method
It is surprising that the salts of 3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide can be obtained in extremely pure form (>99% purity in all cases). That's true. For it was completely unexpected that a simple extraction of the organic phase with water or dilute aqueous sulfuric acid would remove virtually all troublesome impurities. The preparation of the starting material acetoacetamido-N-sulfonic acid and its salts is preferably carried out by combining the Li- or ammonium salt of amidosulfonic acid with diketene according to step (a) of the process of European Patent Application No. 85102885.2 mentioned above. This is carried out by reaction in an inert organic solvent. In this way a solution of the Li and ammonium salt of acetoacetamido-N-sulfonic acid is obtained, which can be used as such directly in the cyclization reaction with SO ₃ . Of course, it is also possible to use other salts of acetoacetamido-N-sulfonic acid, in particular alkali metal and alkaline earth metal salts, in the cyclization reaction described above. Compared to the use of these salts,
The use of free acetoacetamido-N-sulfonic acid provides little benefit. As in the case of the salt, the free acetoacetamido-N-sulfonic acid can also be used directly in the cyclization reaction as a suitable solution as obtained in its preparation. German patent application P3410440.2
Free acetoacetamide probably produced as an intermediate in the method of (Japanese Patent Application No. 60-54718)
Solutions of N-sulfonic acid can also be regarded as solutions such as those obtained during its preparation. As inert organic solvents for acetoacetamido-N-sulfonic acid or its salts, the series of inert organic solvents listed in the aforementioned patent applications are suitable, which are immiscible with water; , halogenated aliphatic hydrocarbons, preferably those having up to 4 carbon atoms, such as for example methylene chloride, chloroform, 1,2-dichloroethane, trichlorethylene, tetrachlorethylene, trichlorofluoroethylene, etc.; lower aliphatic Carbonic esters of alcohols, preferably methanol or ethanol; nitroalkanes, preferably those having up to 4 carbon atoms, especially nitromethane; and alkyl-substituted pyridines, preferably collidine, and the like. These organic solvents can be used individually or as mixtures. Particularly preferred solvents are halogenated aliphatic hydrocarbons, especially methylene chloride. The concentration of acetoacetamido-N-sulfonic acid or its salt in the inert solvent is not critical, but is limited on the one hand by solubility and on the other hand by economic considerations. This is because at higher dilutions a larger amount of solvent has to be separated off and purified again afterwards. Generally acetoacetamide per unit
A concentration of about 0.1 to 2 molar N-sulfonic acid or its salt is preferred. SO ₃ can be in solid or liquid form or
It can also be added by condensing SO ₃ vapor. However, it is preferably added in dissolved form, in particular in an inert organic or inert inorganic solvent that is immiscible with water. In principle, the water-immiscible inert organic solvent is the same as that used for dissolving acetoacetamido-N-sulfonic acid or its salt. As inert inorganic solvent, for example concentrated sulfuric acid or liquid SO ₂ can be used. The amount of inert solvent used for SO ₃ is also not critical in principle. If a solvent is used, it is only necessary to ensure that the SO ₃ is properly dissolved, the upper limit being set by the amount of solvent due to economic considerations. An advantageous concentration is about 5 to 50% by weight SO ₃ , preferably about 15 to 30% by weight. In a preferred embodiment of the invention, the same inert solvent is used both for acetoacetamido-N-sulfonic acid or its salts and for SO ₃ , preferably only halogenated aliphatic hydrocarbons, especially methylene chloride. sell. The molar ratio of acetoacetamido-N-sulfonic acid or acetoacetamido-N-sulfonate to _SO3 can be about 1:1, but up to about 20 times
An excess of SO ₃ is preferred, preferably about 3-fold to 10-fold, and a molar excess of about 4-fold to 7-fold. Carrying out the cyclization reaction is otherwise carried out as described in 3 above.
in the same manner and under the same conditions as described in the patent application. When acetoacetamido-N-sulfonic acid or its salt and -SO ₃ are used in equimolar amounts, as is clear from the reaction scheme shown at the beginning,
“SO ₃ adduct” is not generated. Therefore, hydrolysis is not necessary in this case. If starting compounds dissolved in an inert organic solvent are used, the reaction mixture constitutes an organic phase, which can be dissolved without subsequent separation operations.
or in some cases after removal of precipitated salts.
It can be immediately recycled for further processing according to the invention. If starting material SO ₃ dissolved in an inert inorganic solvent, such as concentrated sulfuric acid, is used, the organic phase has to be separated off appropriately after the cyclization reaction has ended. In the preferred case where acetoacetamido-N-sulfonic acid or its salt and SO ₃ are used in a molar ratio of 1:1 or more, an “SO ₃ adduct” is formed in the cyclization reaction, and from this a “SO 3 adduct” is formed which can be removed by hydrolysis. Therefore 6-methyl-3,4-dihydro-1,2,3
- It is necessary to liberate oxathiazin-4-one-2,2-dioxide. Hydrolysis is carried out using water or ice, preferably - used SO ₃
With respect to excess - in a molar ratio of about 2 to 6 times,
This is done by adding After hydrolysis, then two phases or (if 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide has already precipitated) A three-phase mixture exists. 6-methyl-3,4-dihydro-1,
The 2,3-oxathiazin-4-one-2,2-dioxide is present substantially dissolved in the organic phase and the sulfuric acid phase. The organic phase is then separated. Preferably, the aqueous sulfuric acid phase contains the optionally precipitated 6-methyl-3,4-dihydro-1,
Extraction with 2,3-oxathiazin-4-one-2,2-dioxide - or with an inert organic solvent immiscible with water - especially with the same solvent in which the cyclization reaction was also carried out. and the extract is combined with the previously separated organic phase. The inert organic solvent used for the cyclization reaction is described, for example, in German patent application P3527050.5
6-Methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2- Dioxide exists mainly dissolved only in the sulfuric acid phase. In this case, 6-methyl-3,4-dihydro-1,2,3
-Oxathiazin-4-one-2,2-dioxide will have to be extracted as completely as possible again for the purification operation according to the invention with an inert organic solvent of the type already described above. The aqueous sulfuric acid phase, or the organic phase separated from the reacting combined organic phases, is then purified by extraction with a fairly small amount of water or dilute aqueous sulfuric acid, although purification with water alone is preferred. If dilute aqueous sulfuric acid is used for purification, its concentration is
Preferably it is about 2 to 20%. The volume ratio of organic to aqueous or aqueous sulfuric acid extraction phase is generally about (20-5):1. However, effective purification can often still be achieved even with fairly small amounts of water. The extraction is carried out in the simplest case by stirring the two phases in a stirred flask or stirred vessel; specific equipment includes basically all industrial extraction equipment, e.g.
Settler equipment, screen plate tower, packed tower,
A Karr tower or the like is suitable. Mixing devices, such as static mixers, may also be used to enhance contact between the extraction phases. Extraction can be carried out either batchwise or continuously. Extracted 6-methyl-3,4-dihydro-
1,2,3-oxathiazin-4-one-2,2
- The proportion of dioxide is generally about 2 to 30% by weight, depending on the amount of water used. aqueous phase (relatively small amount of extracted 6-methyl-3,4-
Recirculating the dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide) to the hydrolysis of the " _SO3 adduct" is beneficial for the economical operation of the overall process. is important. This can be carried out either batchwise or continuously. From the purified organic phase or from the combined purified organic phases, 6-methyl-
A non-toxic salt of 3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide is obtained. Bases suitable for this purpose are those containing non-toxic cations. Potassium bases (solutions such as KOH, KHCH ₃ , K ₂ CO ₃ etc.) are preferred, with KOH being particularly preferred. 6-methyl-3,4-dihydro-1,2,3-
Neutralization of oxathiazin-4-one-2,2-dioxide and 6-methyl-3,4-dihydro-
1,2,3-oxathiazin-4-one-2,2
- Isolation of its non-toxic salts from the purified organic phase containing the dioxide can be carried out, for example, by evaporating the organic phase, absorbing the residue in water or lower aliphatic alcohols and converting this solution into an aqueous or aqueous-alcoholic solution. Advantageously, by neutralizing with a base and crystallizing this solution, or alternatively by bringing about e.g. a strong contact between the purified organic phase or the corresponding combined organic phase and the aqueous alkaline solution. It will be held in Intense contacting is generally carried out in conventional equipment, as already mentioned above, using processes customary for this purpose, depending on the mode and method of extraction. Mixing devices such as static mixers can also be used for this purpose. During neutralization, the hydroalcoholic phase is generally
Sufficient base is added so that the PH, or pure aqueous phase, reaches a value of about 5 to 12, preferably 8 to 11. 6-Methyl-3,4-dihydro-
1,2,3-oxathiazin-4-one-2,2
- Dioxide salts are the usual method (by crystallization)
isolated in If, for example, a strong contact is carried out between the purified organic phase and the aqueous base for neutralization, about 1 to 10%, preferably about 4 to 8%
If dilute aqueous KOH with a concentration of K precipitates. Neutralization is more concentrated aqueous KOH—i.e.
When carried out with a potassium hydroxide solution having a concentration of 10 to 50%, preferably about 20 to 35%, a portion of the acetyl fume K produced is mixed with the potassium hydroxide solution and a suitable purified During intensive contact with the organic phase, it crystallizes immediately without further treatment. This product also typically has a purity of 99.5% or higher. Acetyl fume K
The remainder is obtained by concentrating and optionally cooling the aqueous solution. It is advantageous to carry out the above two neutralization steps in such a way that a strong contact between the aqueous base and the organic phase takes place very rapidly - preferably from about 1 to 60 seconds, especially from about 2 to 10 seconds. It is. This means that
This has the effect of increasing the space-time yield at this stage.
Apparatus suitable for this purpose include thin film reactors,
There is a falling film reactor or mixing device. 6-methyl-3,4-dihydro-1,2,3-
Another preferred embodiment of the neutralization of oxathiazin-4-one-2,2-dioxide is to evaporate the organic solvent from the (purified) organic phase containing this compound with simultaneous addition of water, and 6-Methyl-3,4-dihydro-1,2,3-oxathiazin-4-one- thus obtained
It consists in neutralizing an aqueous solution of 2,2-dioxide with a base, preferably a potassium base and especially KOH. However, this embodiment works well only if the organic phase involved contains a solvent with a boiling point (at normal pressure) below 100°C.
This is because otherwise the disposed water would immediately evaporate upon condensation with the solvent. Preferred devices for this embodiment are devices for rapid evaporation, such as, for example, thin film evaporators or falling film evaporators. Yet another preferred embodiment of the present invention is
From the (purified) organic phase containing 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide, the organic solvent is removed simultaneously with an aqueous base, preferably an aqueous base. It consists in neutralizing the above compounds by evaporation while adding potassium base and especially aqueous KOH. This embodiment also works well only if the organic solvent has a boiling point (at normal pressure) below 100°C. Preferred devices for this embodiment are also devices for rapid evaporation, such as, for example, thin film evaporators or falling film evaporators. The product obtained in this case is a heated aqueous solution from which, by cooling and optionally evaporating, 6-methyl-3,4-dihydro-1,
A salt of 2,3-oxathiazin-4-one-2,2-dioxide crystallizes out. In all the above embodiments of the neutralization step,
6-Methyl-3,4 present in the organic phase before neutralization
-dihydro-1,2,3-oxathiazine-4-
Yields (=degree of isolation) of about 80 to 90% can be achieved in all cases with regard to the 1-2,2-dioxide. If desired, the yield can be further improved by further evaporating the aqueous phase obtained after removal of acesulfame K. For the starting material acetoacetamido-N-sulfonic acid or acetoacetamido-N-sulfonate, the yield is lower by a factor of the yield of the reaction. In order to meet the highest purity requirements, it is also possible to recrystallize acesulfame K from water, optionally in the presence of activated carbon. The following examples are intended to explain the invention in more detail. In each example, 6-methyl-3,
4-dihydro-1,2,3-oxathiazine-4
-one-2,2-dioxide is abbreviated as "ASH" and its potassium salt is abbreviated as "ASK". Preparation of the starting material acetoacetamide-N-sulfonate used in each example 97.1 g (1.0 mol) of amidosulfonic acid were suspended in 1.0 methylene chloride. 106 g (1.05 mol) of triethylamine were added while stirring, the amidosulfonic acid being dissolved as the triethylammonium salt. After addition of 6 g (0.1 mol) of glacial acetic acid, 97% diketene was added dropwise within 1 hour at an internal temperature of 15° C. while stirring. According to HPLC (high pressure liquid chromatography) analysis, the yield of acetoacetamide-N-sulfonate was 90%. The solution thus obtained was used directly in the subsequent reactions. Example 1 Cyclization and Hydrolysis 400 ml of a 15% solution of SO ₃ in CH ₂ Cl ₂ was precharged into a round bottom flask and blanketed with nitrogen. At an internal temperature of -30°C (isopropanol/dry ice cooling:
-40°C to -50°C), ₁₅ % of _SO3 / _CH2Cl2 under stirring
1850 ml of solution and simultaneously the above solution of acetoacetamide-N-sulfonate in CH ₂ Cl ₂ were added dropwise over a period of 25 minutes. Hydrolysis was carried out by adding 500 ml of water dropwise over a period of about 30 minutes starting at -30° C. with intensive external cooling. During this time the temperature is -
The temperature rose rapidly from 30°C to 0°C, and then remained at 0°C to +5°C. Preparation of ASH/Methylene Chloride Solution The organic phase was separated at 5° C. and the aqueous sulfuric acid phase was extracted twice more with 1.0 CH ₂ Cl ₂ . Thereby a solution of 132 g of ASH in 5.0 methylene chloride (=1.9
% solution) was obtained. Yield: 81% (with respect to amidosulfonic acid). Separation of ASK Add 2.5 of this ASH/methylene chloride solution to 250 ml of water.
was added and stirred for 2 hours. The organic phase was evaporated under reduced pressure. The residue was dissolved in the same weight of methanol and then adjusted to pH 8-10 with 20% KOH/methanol.
(=KOH/methanol precipitation). After filtering and drying, 69.5 g of ASK were isolated (yield=85% with respect to 66 g of ASH used). Analytical value: ASK K ₂ SO ₄ 99.6% 0.4% Comparison: 2.5% of the 1.9% ASH/methylene chloride solution prepared as described above was evaporated under reduced pressure without further purification. The residue was dissolved in the same weight of methanol and then the PH was adjusted to 8-10 using 20% KOH/methanol. After filtering and drying, 96.5 g of crude ASK were isolated (yield: 98% with respect to 66 g of ASH used). This one is 83%
The K ₂ SO ₄ content was 8.8% (with respect to ASK). Example 2 Recirculation of the aqueous phase obtained during extraction of the organic ASH phase with water to the hydrolysis stage. An amount corresponding to 1/10 in each case of the amount of starting material stated in Example 1 was used for the cyclization reaction. obtained
The ASH/methylene chloride solution (500ml) was then stirred with 50ml each of water for 2 hours. The aqueous phase thus obtained was used for hydrolysis in the following experiments. After 10 experiments in which the aqueous phase was recycled 9 times, the ASK samples listed in Table 1 were isolated by KOH/methanol precipitation (see Example 1).

【table】

Table Example 3 Extractive neutralization of the ASH/methylene chloride phase with a 7% caustic potassium solution. 500 ml of water was added to 5.0 ml of the 1.9% ASH/methylene chloride solution prepared according to Example 1 and stirred for 2 hours. The organic phase (containing 112 g of ASH) was separated and stirred for 1.5 hours with 600 g of 7% caustic potassium solution. The aqueous phase was then separated. 490 g of water were removed from this solution by distillation under reduced pressure (60 mbar). After cooling the residue to 0° C., 115.7 g of ASK was isolated and the product was separated and dried. Yield: 87% (on 112g ASH). Analytical value: ASK K ₂ SO ₄ 99.9% 0.05% After further evaporation of the crystallization mother liquor, 13.0 g of
ASK was isolated. Yield: 9% (on 112g ASH). Analytical values: ASK K ₂ SO ₄ 99.8% 0.3% Example 4 Extractive neutralization of the ASH/methylene chloride phase with a 30% caustic potassium solution in a stirred flask. 500 ml of water was added to 5.0 ml of the ASH/methylene chloride solution prepared according to Example 1 and stirred for 2 hours. Separate the organic phase (=ASH112g) and add 30% KOH144.0
g and stirred for 0.5 hour. The reaction mixture was then filtered. After drying, 112.8 g of ASK was obtained. Yield: 81.5% (on 112g ASH). Analysis value: ASK K ₂ SO ₄ 99.8% 0.1% Example 5 ASH/methylene chloride phase in thin film reactor
Extractive neutralization with 30% caustic potash solution. The apparatus consisted of a commercially available laboratory thin film evaporator with an effective length of 22 cm and an effective surface area of 160 ^cm2 ;
It was operated as a thin film reactor. 2.5 g of ASH/methylene chloride solution treated with water as described in Example 4 and 65.4 g of 30% KOH were pumped simultaneously over 1 hour (rotor speed approx.
800r.pm). The ASK produced was separated from the reaction mixture leaving the reactor by means of a suction funnel. After drying,
ASK56.1g was obtained. Yield: 81% (regarding ASH56g). Analytical amount: ASK K ₂ SO ₄ 99.7% 0.3% The average residence time was 2.5 seconds, calculated from the dead space in the reactor and the volumetric flow rate supplied. Example 6 Distillation of CH ₂ Cl ₂ under addition of water in a thin film evaporator. The apparatus consisted of a commercially available laboratory thin film evaporator with an effective length of 22 cm and an effective surface area of 160 cm ² . water as described in Example 3
500 ml of ASH/CH ₂ Cl ₂ solution (ASH 112 g) 5.0/h and water 180 g/h,
Simultaneously entered the evaporator at a heating jacket temperature of 115°C. Approximately 60% of the water leaving the evaporator
After cooling the ASH/water solution to room temperature, it was neutralized with 78.5 g of 50% caustic potassium solution under stirring.
After cooling the mixture to 0° C., 110.7 g of ASK was isolated. Yield: 80% (on 112g ASH). Analytical value: ASK K ₂ SO ₄ 99.9% 0.2% After further evaporation of the crystallization mother liquor, 12.0 g of
ASK was isolated. Yield: 9% (on 112g ASH). Analytical values: ASK K ₂ SO ₄ 99.7% 0.3% Example 7 Under the addition of caustic potash in a thin film evaporator
_Distillation of _CH2Cl2 . In the same apparatus as described in Example 6,
Same as example 6, at a heating medium temperature of 115 °C
5.0/h of ASH/CH ₂ Cl ₂ solution and 250 g of 16% caustic potash solution were fed simultaneously. Evaporator (T=105
A homogeneous aqueous solution of ASK flowed out (°C). After cooling the solution to 0° C., the crystallized ASK was separated off and dried under reduced pressure. Yield: 127.2g (92%) (regarding ASH112g) Analysis value: ASK K ₂ SO ₄ 99.9% 0.1%

Claims (1)

[Claims] 1. 6-Methyl-3,4-dihydro-1,2,3-oxathiazin-4-one- by cyclization of an acetoacetamide derivative and neutralization with a base.
A method for producing non-toxic salts of 2,2-dioxide, using acetoacetamide-N-sulfonic acid or a salt thereof dissolved in an inert organic solvent immiscible with water as the acetoacetamide derivative; carrying out the cyclization by the action of at least about equimolar amounts of SO ₂ , optionally dissolved in an inert organic or inert inorganic solvent which is also immiscible with water; When more than equimolar amount of SO ₃ is used,
After the cyclization reaction, hydrolyzing the 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide obtained as an SO ₃ adduct, present or Purifying the organic phase that separates during hydrolysis by extraction with a relatively small amount of water or dilute aqueous sulfuric acid, and from the organic phase so purified by neutralization with a base, the 6-methyl-3 ,4-dihydro-1,2,3-oxathiazin-4-one-2,
6-Methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2, characterized in that the non-toxic salt of 2-dioxide is isolated.
A method for producing a non-toxic salt of 2-dioxide. 2. Process according to claim 1, using a solution of acetoacetamido-N-sulfonic acid or its salt and _SO2 in the same water-immiscible inert organic solvent. 3. The method according to claim 1 or 2, wherein the cyclization is carried out by the action of SO ₃ in an equimolar or more amount with respect to acetoacetamido-N-sulfonic acid or its salt. 4 6-methyl-3,4-dihydro-1,2,3
- the aqueous sulfuric acid phase that forms during the hydrolysis of the oxathiazin-4-one-2,2-dioxide adduct - optionally precipitated 6-methyl-3,4-
dihydro-1,2,3-oxathiazin-4-one-2,2-dioxide - again extracted with an inert organic solvent immiscible with water and this organic extract separated during hydrolysis. 4. A method according to any one of claims 1 to 3, in which the organic phase is combined with an organic phase. 5. The water used for the extractive purification of the organic phase or the dilute aqueous sulfuric acid likewise used is again 6-methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2,2- 5. A process according to claims 1 to 4, in which the adduct of the dioxide is recycled to the hydrolysis. 6 6-Methyl-3,4-dihydro-1,2,3-oxathiazin-4-one-2, from the purified organic phase containing free dioxide compounds.
A process according to any one of claims 1 to 5, characterized in that the non-toxic salt of 2-dioxide is isolated by evaporating the organic phase and neutralizing the residue with a base. . 7 6-methyl-3,4-dihydro-1,2,3
-Oxathiazin-4-one-2,2-dioxide is neutralized by intensive contact of the purified organic phase containing this compound with an aqueous base. The method described in any of the paragraphs. 8 6-methyl-3,4-dihydro-1,2,3
In order to neutralize this compound from the purified organic phase containing -oxathiazin-4-one-2,2-dioxide, the organic solvent was evaporated with simultaneous addition of water and 6-methyl -3,4
-dihydro-1,2,3-oxathiazine-4-
6. The method according to claim 1, wherein an aqueous solution of 1-2,2-dioxide is neutralized with a base. 9 6-methyl-3,4-dihydro-1,2,3
- In order to neutralize this compound from the purified organic phase containing oxathiazin-4-one-2,2-dioxide, the organic solvent is evaporated with simultaneous addition of an aqueous base. Range 1
5. The method according to any one of items 5 to 5. 10. Process according to claim 8 or 9, in which the removal of the organic solvent by evaporation with simultaneous addition of water or an aqueous base is carried out in a thin film evaporator or a falling film evaporator.